Lotoproxen

Uses

Lotoproxen is used for the relief of symptoms of rheumatoid arthritis, both of acute flares and long term management of the disease. It is also used in the diseases of rheumatoid osteoarthritis (degenerative arthritis), ankylosing spondylitis, juvenile rheumatoid arthritis, tendinitis, brusitis, acute gout, acute musculoskeletal disorders (such as sprains, direct trauma and fibrositis), migraine and dysmenorrhoea.

Lotoproxen is also used to associated treatment for these conditions: Acute Gouty Arthritis, Acute Migraine, Ankylosing Spondylitis (AS), Arthritis, Backache, Bursitis, Extra-Articular Rheumatism, Fever, Flu caused by Influenza, Headache, Juvenile Idiopathic Arthritis (JIA), Menstrual Distress (Dysmenorrhea), Migraine, Muscle Spasms, Nasal Congestion, Osteoarthritis (OA), Pain, Post-traumatic pain, Postoperative pain, Primary Dysmenorrhoea, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Seasonal Allergic Rhinitis, Sinusitis, Tendinitis, Toothache

How Lotoproxen works

As with other non-selective NSAIDs, naproxen exerts it's clinical effects by blocking COX-1 and COX-2 enzymes leading to decreased prostaglandin synthesis. Although both enzymes contribute to prostaglandin production, they have unique functional differences. The COX-1 enzymes is constitutively active and can be found in normal tissues such as the stomach lining, while the COX-2 enzyme is inducible and produces prostaglandins that mediate pain, fever and inflammation. The COX-2 enzyme mediates the desired antipyretic, analgesic and anti-inflammatory properties offered by Lotoproxen, while undesired adverse effects such as gastrointestinal upset and renal toxicities are linked to the COX-1 enzyme.

Dosage

Lotoproxen dosage

Tablet & Suppository (Adult)-

• Rheumatic disorders:The usual initial dose of naproxen is 250 mg twice daily adjusted to 500 mg to 1000 mg daily in 2 divided doses.
• Juvenile arthritis: A dose of 10 mg/kg body weight daily in 2 divided doses is used for children over 5 years of age.
• Acute gout: An initial dose of 750 mg followed by 250 mg every 8 hours.
• Dysmenorrhoea: 500 mg may be given initially followed by 250 mg in every 6-8 hours.

Syrup (Children over 5 years)-

• In juvenile arthritis: The usual dosage of Lotoproxen is 10 mg/kg/day taken in two doses at 12-hour intervals is recommended.

Gel:Lotoproxen gel is to be applied 2-6 times a day as required and is not recommended for use in children.

Side Effects

Gastro-intestinal discomfort: nausea, diarrhoea and occasionally bleeding and ulceration.

Hypersensitivity reactions: notably with bronchospasm, rashes and angioedema.

CNS side effect: drowsiness, headache, fluid retention, vertigo, hearing disturbances such as tinnitus, photosensitivity.

A few instances of jaundice, impairment of renal function, thrombocytopenia, and agranulocytosis have been reported.

Toxicity

Although the over-the-counter (OTC) availability of naproxen provides convenience to patients, it also increases the likelihood of overdose. Thankfully, the extent of overdose is typically mild with adverse effects normally limited to drowsiness, lethargy, epigastric pain, nausea and vomiting. Although there is no antidote for naproxen overdose, symptoms will typically subside with appropriate supportive care.

Lotoproxen is classified as Category B during the first 2 trimesters of pregnancy, and as Category D during the third trimester. Lotoproxen is contraindicated in the 3rd trimester since it increases the risk of premature closure of the fetal ductus arteriosus and should be avoided in pregnant women starting at 30 weeks gestation.

Precaution

Lotoproxen should be used with caution in patients with cardiac, hepatic and renal impairment, coagulation defect, and previous history of gastro-intestinal ulceration. The drug is contraindicated in patients with a history of hypersensitivity to aspirin or any other NSAID - which includes those in whom attacks of asthma, angioedema, urticaria or rhinitis have been precipitated by aspirin or any other NSAID.

Interaction

Antacid: The absorption of naproxen can be altered by antacids.

Aspirin: Plasma concentration of Lotoproxen can be reduced when aspirin is given concomitantly, this appeared to be due to increased exeretion of naproxen.

Diuretics: Lotoproxen diminish the effect of frusemide.

Probenecid: It increase the plasma concentration of Lotoproxen.

Food Interaction

• Take with food. Food reduces GI irritation.

Lotoproxen Alcohol interaction

[Moderate] GENERALLY AVOID:

The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss.

The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

Lotoproxen Hypertension interaction

[Major] Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Therapy with NSAIDs should be administered cautiously in patients with preexisting fluid retention, hypertension, or a history of heart failure.

Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

[Moderate] Anaprox and Anaprox DS (brands of naproxen sodium) contain 25 mg and 50 mg of sodium per tablet (approximately 1 mEq<250 mg naproxen), respectively, and Naprosyn suspension contains 39 mg per teaspoonful (approximately 1.5 mEq<125 mg naproxen).

The sodium content should be considered when these products are used in patients with conditions that may require sodium restriction, such as congestive heart failure, hypertension, and fluid retention.

[Moderate] Nonsteroidal anti-inflammatory drugs (NSAIDs), including topicals, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events.

NSAIDs should be used with caution in patients with hypertension.

Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the course of therapy.

Lotoproxen Drug Interaction

Moderate: aspirin, duloxetine, omega-3 polyunsaturated fatty acids, escitalopram, esomeprazole, sertralineUnknown: amphetamine / dextroamphetamine, diphenhydramine, cyclobenzaprine, fluticasone nasal, pregabalin, acetaminophen / hydrocodone, montelukast, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol, alprazolam, cetirizine

Lotoproxen Disease Interaction

Major: asthma, fluid retention, GI toxicity, rash, renal toxicities, thrombosisModerate: sodium, anemia, heart failure, hepatotoxicity, hyperkalemia, hypertension, platelet aggregation inhibition

Volume of Distribution

Lotoproxen has a volume of distribution of 0.16 L/kg.

Elimination Route

Lotoproxen is available as a free acid and sodium salt. At comparable doses, (naproxen 500 mg = naproxen sodium 550 mg) they differ slightly in their rates of absorption, but otherwise they are therapeutically and pharmacologically equivalent. Lotoproxen sodium achieves a peak plasma concentration after 1 hour, while peak plasma concentration is observed after 2 hours with naproxen (free acid). There are no differences between the 2 forms in the post-absorption phase pharmacokinetics. The difference in initial absorption should be considered when treating acute pain, since naproxen sodium may offer a quicker onset of action.

The mean Cmax for the various formulations (immediate release, enteric coated, controlled release etc.) of naproxen are comparable and range from 94 mcg/mL to 97.4 mcg/mL. In one pharmacokinetic study, the mean Tmax of naproxen 500 mg (immediate release) given every 12 hours over 5 days was 3 hours, compared to a mean Tmax of 5 hours for Naprelan 1000 mg (controlled release) given every 24 hours over 5 days. In this same study, the AUC_0-24hr was 1446mcgxhr/mL for naproxen immediate release and 1448 mcgxhr/mL for the controlled release formulation. A separate study comparing the pharmacokinetics of Naprosyn tablets and EC-Naprosyn observed the following values: Tmax and AUC_0-12hrs of EC-Naprosyn were 4 hours and 845 mcgxhr/mL respectively, and Tmax and AUC_0-12hrs values of Naprosyn were 1.9 hours and 767 mcgxhr/mL respectively.

When given in combination with sumatriptan the Cmax of naproxen is roughly 36% lower compared to naproxen sodium 550 mg tablets, and the median Tmax is 5 hours.

Based on the AUC and Cmax of naproxen, Vimovo (naproxen/esomeprazole combination product) and enteric-coated naproxen may be considered bioequivalent.

Overall, naproxen is rapidly and completely absorbed when administered orally and rectally. Food may contribute to a delay in the absorption of orally administered naproxen, but will not affect the extent of absorption.

Half Life

The elimination half-life of naproxen is reported to be 12-17 hours.

Clearance

Lotoproxen is cleared at a rate of 0.13 mL/min/kg.

Elimination Route

After oral administration, about 95% of naproxen and it's metabolites can be recovered in the urine with 66-92% recovered as conjugated metabolite and less than 1% recovered as naproxen or desmethylnaproxen. Less than 5% of naproxen is excreted in the feces.

Pregnancy & Breastfeeding use

There are no well controlled studies in pregnant women. The drug should not be used during pregnancy unless clearly needed. Because of the possible adverse effects of prostaglandin inhibiting drugs on neonates, use in nursing mothers must be avoided.

Contraindication

Lotoproxen suppository in contraindicated in children under 12 years of age. The suppository is contraindicated also in patients with any inflammatory lesions of rectum or anus and in patients with recent history of rectal or anal bleeding.

Acute Overdose

Significant overdosage of the drug may be characterized by drowsiness, heartburn, indigestion, and nausea or vomiting. It is not known what dose of the drug would be life threatening.

Storage Condition

Tablet: Protect from light and store below 30° C temperature in a dry place.

Suppository: Store below 25°C temperature.

Gel: Store in a cool and dry place protected from light.

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